Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population

Abstract

Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.